Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

June 17, 2016 updated by: O'Dorisio, M S

A Phase I, Open Label, Maximum Tolerated Dose-Finding Study to Evaluate the Safety and Tolerability of 90Y-DOTA-tyr3-Octreotide Administered by Intravenous Infusion to Children With Refractory Somatostatin-Receptor Positive Tumors

RATIONALE: Radiolabeled octreotide can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is to study the safety and effectiveness of radiolabeled octreotide in treating children who have advanced or refractory solid tumors.

Study Overview

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of yttrium Y 90-DOTA-tyr3-octreotide in children with advanced or refractory somatostatin receptor-positive tumors.
  • Determine the short-term and long-term safety and the serious adverse-event profiles of this drug in these patients.
  • Determine any potential antitumor effect of this drug in these patients.
  • Correlate level of somatostatin receptor type 2 expression with response in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive yttrium Y 90-DOTA-tyr3-octreotide IV over 5-10 minutes on day 1. Treatment repeats every 6 weeks for up to 3 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of yttrium Y 90-DOTA-tyr3-octreotide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly after each treatment course, 6 weeks after the last course, and then every 6 months thereafter for life.

PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Iowa
      • Iowa City, Iowa, United States, 52242-1002
        • Holden Comprehensive Cancer Center at University of Iowa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed malignant neoplasm

    • Not amenable to standard therapy or has failed existing first- and second-line therapies
  • Tumor positive for somatostatin receptors by OctreoScan within the past 4 weeks
  • At least 1 measurable lesion

    • Lesions that have been previously irradiated must demonstrate progression since radiation
    • At least 1 measurable somatostatin receptor-positive lesion that has not been irradiated within the past 4 weeks AND has not had full craniospinal radiation within the past 3 months
  • Bone marrow with at least 40% cellularity OR at least 20% cellularity with one million CD34+ stem cells/kg stored
  • No diffuse bone marrow involvement by OctreoScan scintigraphy

PATIENT CHARACTERISTICS:

Age

  • 2 to 25

Performance status

  • COG 0-2 OR
  • Karnofsky 60-100% OR
  • Lansky 60-100%

Life expectancy

  • 2-12 months

Hematopoietic

  • See Disease Characteristics
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin less than 1.5 times normal
  • AST and ALT less than 2.5 times upper limit of normal

Renal

  • Creatinine no greater than 1 mg/dL (children less than 5 years of age)
  • Creatinine less than 1.2 mg/dL (children 5 to 10 years of age)
  • Creatinine less than 1.7 mg/dL (children over 10 years of age) AND
  • Glomerular filtration rate at least 80 mL/min/m^2

Cardiovascular

  • Shortening fraction at least 28% by echocardiogram
  • Ejection fraction at least 50% by bi-plane method of echocardiogram
  • No prior congestive heart failure unless ejection fraction at least 40%
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No symptomatic congestive heart failure

Other

  • No other concurrent malignancy
  • No other significant uncontrolled medical, psychiatric, or surgical condition that would preclude study compliance
  • No antibodies to yttrium Y 90-DOTA-tyr3-octreotide or octreotide
  • No prior allergic reactions to compounds of similar chemical or biologic composition to yttrium Y 90-DOTA-tyr3-octreotide
  • No ongoing or active infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

  • More than 28 days since prior long-acting somatostatin analogues
  • No concurrent somatostatin analogues 12 hours before or 12 hours after study drug administration
  • Concurrent hormonal therapy (other than somatostatin analogue) allowed provided patient received hormonal therapy for at least 2 months and has stable disease or progressive disease

Radiotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • No prior radiotherapy to 25% or more of bone marrow
  • No prior external beam radiotherapy to both kidneys (scatter doses of less than 500 cGy to a single kidney or radiation to less than 50% of a single kidney is allowed)

Surgery

  • At least 4 weeks since prior surgery

Other

  • Recovered from prior therapy
  • At least 4 weeks since prior investigational drugs
  • No other concurrent approved or investigational anti-neoplastic therapies except for bisphosphonates
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 90Y-DOTA-tyr3-OCTREOTIDE
Dose escalation will proceed so that the single-cycle and three-cycle maximum tolerated doses of 90Y-DOTA-tyr3-Octreotide can be determined. The initial dose of 90Y-DOTA-tyr3-Octreotide to be administered is 30 mCi/m2 in each of three cycles. Dose escalation will proceed in 10 mCi/m2 intervals and will be permitted for the next cohort of subjects pending completion of Cycle 3 by 2 members of the previous cohort with no DLTs. A DLT is defined as a Grade 3 renal toxicity, Grade 4 bone marrow toxicity, or any other Grade 3 toxicity whether or not related to study drug and regardless of duration. Lymphopenia will not be used to define a DLT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide
Time Frame: 6 weeks per cycle
Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors based upon the 6 week/cycle dose-limiting-toxicity profile.
6 weeks per cycle
Evaluate the short term and long term safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events)
Time Frame: short term (6 weeks/cycle); long term (4-6 mos./cycle)
2. Evaluate the short-term (6 weeks/cycle) and long term (4-6 months) safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events) serious adverse event profile of three-cycles of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors.
short term (6 weeks/cycle); long term (4-6 mos./cycle)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: M. Sue O'Dorisio, MD, PhD, Holden Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2002

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2011

Study Registration Dates

First Submitted

November 12, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 21, 2016

Last Update Submitted That Met QC Criteria

June 17, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • 200008086
  • UIHC-200008086
  • NCI-V02-1710

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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